Abstract
BackgroundTreatment of frail patients with advanced colorectal cancer (CRC) is controversial. This pilot phase II trial aimed to assess the efficacy and safety of regorafenib when administered in first-line to frail patients with advanced CRC.MethodsFrail patients without prior advanced colorectal cancer treatment were included in the study. Definition of frailty was defined per protocol based on dependency criteria, presence of chronic comorbid pathologies and/or geriatric features. Main objective: to assess progression-free survival (PFS) rate at 6 months. Treatment consisted of 28-day cycles of orally administered regorafenib 160 mg/day (3 weeks followed by 1 week rest).ResultsForty-seven patients were included in the study. Median age was 81 years (range 63–89). Frailty criteria: dependency was observed in 26 patients (55%), comorbidities in 27 (57%) and geriatric features in 18 (38%). PFS rate at 6 months was 45% (95% confidence interval [CI] 30–60]. Median PFS was 5.6 months (95%CI 2.7–8.4). Median overall survival (OS) was 16 months (95%CI 7.8–24). Complete response, partial response and stable disease were observed in one, two and 21 patients respectively (objective response rate 6.4%; disease control rate 51%). Thirty-nine patients (83%) experienced grade 3–4 adverse events (AEs). The most common grade 3–4 AEs were hypertension (15 patients; 32%), asthenia (14; 30%), hypophosphatemia (6; 13%); diarrhea (4; 8%), hand-foot-skin reaction (4; 8%). There were two toxic deaths (4.2%) (grade 5 rectal bleeding and death not further specified). Dose reduction was required in 26 patients (55%) and dose-delays in 13 patients (28%).ConclusionsThe study did not meet the pre-specified boundary of 55% PFS rate at 6 months. Toxicity observed (83% patients experienced grade 3 and 4 AEs) preclude its current use in clinical practice on this setting. Disease control rate and overall survival results are interesting and might warrant further investigation to identify those who benefit from this approach.Trial registrationThis trial was prospectively registered at EudraCT (2013–000236-94). Date of trial registration: April 9th, 2013.
Highlights
Treatment of frail patients with advanced colorectal cancer (CRC) is controversial
Patients and treatment Patients older than 18 with histologically or cytologically proven advanced colorectal adenocarcinoma, without major surgery within 28 days prior to the initiation of study treatment, not previously treated for advanced disease, with measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2, were candidates to be enrolled in the study
This study shows that, when treated with frontline regorafenib, almost half of frail patients with advanced CRC remain progression-free survival (PFS) at 6 months and that this treatment resulted in 16 months median OS
Summary
Treatment of frail patients with advanced colorectal cancer (CRC) is controversial. This pilot phase II trial aimed to assess the efficacy and safety of regorafenib when administered in first-line to frail patients with advanced CRC. Median age at diagnosis of patients with CRC is 71. A significant percentage of these patients are elderly and may be frail, due to either their age itself or comorbid conditions, leading to special vulnerability to treatment toxicity. A few factors such as ageing, dependence for performance of daily activities, associated comorbid conditions, and presence of geriatric features (dementia, delirium, frequent falls, incontinence) are the most important to be taken into account for the definition of frailty [6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
